Sci Immunol . Tissue-resident CD8 + T cells drive age-associated chronic lung sequelae after viral pneumonia

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Sci Immunol


. 2020 Nov 6;5(53):eabc4557.
doi: 10.1126/sciimmunol.abc4557.
Tissue-resident CD8 ⁺ T cells drive age-associated chronic lung sequelae after viral pneumonia


Nick P Goplen ^{1 2} , Yue Wu ³ , Young Min Son ¹ , Chaofan Li ¹ , Zheng Wang ¹ , In Su Cheon ¹ , Li Jiang ¹ , Bibo Zhu ¹ , Katayoun Ayasoufi ³ , Eduardo N Chini ^{2 4} , Aaron J Johnson ³ , Robert Vassallo ¹ , Andrew H Limper ¹ , Nu Zhang ⁵ , Jie Sun ^{6 2 3}



Affiliations

• PMID: 33158975
• DOI: 10.1126/sciimmunol.abc4557

Abstract

Lower respiratory viral infections, such as influenza virus and severe acute respiratory syndrome coronavirus 2 infections, often cause severe viral pneumonia in aged individuals. Here, we report that influenza viral pneumonia leads to chronic nonresolving lung pathology and exacerbated accumulation of CD8⁺ tissue-resident memory T cells (T_RM) in the respiratory tract of aged hosts. T_RM cell accumulation relies on elevated TGF-β present in aged tissues. Further, we show that T_RM cells isolated from aged lungs lack a subpopulation characterized by expression of molecules involved in TCR signaling and effector function. Consequently, T_RM cells from aged lungs were insufficient to provide heterologous protective immunity. The depletion of CD8⁺ T_RM cells dampens persistent chronic lung inflammation and ameliorates tissue fibrosis in aged, but not young, animals. Collectively, our data demonstrate that age-associated T_RM cell malfunction supports chronic lung inflammatory and fibrotic sequelae after viral pneumonia.